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Antiangiogenic mechanisms of simvastatin in retinal endothelial cells.
Hata, Yasuaki; Miura, Muneki; Asato, Ryo; Kita, Takeshi; Oba, Kumiyo; Kawahara, Shuhei; Arita, Ryoichi; Kohno, Ri-ichiro; Nakao, Shintaro; Ishibashi, Tatsuro.
Afiliação
  • Hata Y; Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. hatachan@med.kyushu-u.ac.jp
Graefes Arch Clin Exp Ophthalmol ; 248(5): 667-73, 2010 May.
Article em En | MEDLINE | ID: mdl-20155363
ABSTRACT

BACKGROUND:

While statins have an anti-angiogenic property, their underlying mechanisms are not fully understood. We investigated intracellular mechanisms of simvastatin-mediated reduction in VEGF-induced signalings.

METHODS:

The effects of simvastatin on cell proliferation and viability were evaluated by [(3)H]-thymidine incorporation in retinal endothelial cells (RECs) and cell counting. The impact of simvastatin on VEGF-induced phosphorylation of p44/42 mitogen-activated protein (MAP) kinase, myosin light chain (MLC), and VEGF-receptor (VEGFR) 2 were examined by Western blotting. Involvement of the mevalonate pathway in VEGF-induced signaling was also examined.

RESULTS:

Simvastatin (1 and 10 microM) suppressed VEGF-induced RECs proliferation in a concentration-dependent manner, without affecting cell viability. Simvastatin significantly inhibited VEGF-induced phosphorylation of VEGFR2 and its downstream mediators, p44/42 MAP kinase and MLC. Mevalonate completely reversed VEGF-induced VEGFR2 phosphorylation, but only partially reversed the phosphorylation of p44/42 MAP kinase and MLC.

CONCLUSION:

These data indicate that simvastatin exerts its anti-angiogenic effects through the reduction of VEGFR2 phosphorylation in RECs at least in part. However, there seems to be both mevalonate-dependent and independent pathway in simvastatin's anti-angiogenic property.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Endotélio Vascular / Sinvastatina / Inibidores da Angiogênese Limite: Animals Idioma: En Revista: Graefes Arch Clin Exp Ophthalmol Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Endotélio Vascular / Sinvastatina / Inibidores da Angiogênese Limite: Animals Idioma: En Revista: Graefes Arch Clin Exp Ophthalmol Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Japão